Cognitive and Behavioral Domains That Reliably Differentiate Normal Aging and Dementia in Down Syndrome.
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ABSTRACT:
SUBMITTER: Harp JP
PROVIDER: S-EPMC8468129 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer's disease (AD), however, the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS.Methods: We applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals' disease stage.Results: Decline in tests of memory, sustained attention/motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting that the model is valid.Interpretation: Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion into dementia, or postdiagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.
| S-EPMC5989753 | biostudies-literature
Project description:Background: Apathy has been suggested as a potential predictor of mild cognitive impairment (MCI) progression to dementia. Whether it might predict the transition from normal cognitive function to cognitive impairment has been less studied. The current study aimed to provide a comprehensive summary of the evidence on the association between apathy and the transition from normal cognitive function to cognitive impairment. Methods: We searched the PubMed, Embase, and Web of Science databases for longitudinal prospective cohort studies that evaluated apathy at baseline in the cognitively normal population and had cognitive impairment as the outcome. Random effects models were used, and heterogeneity was explored with stratification. The stability of the synthesized result was indicated using sensitivity analysis by excluding one study each time and recalculating the overall effect. Results: Ten studies comprising 26,195 participants were included. Apathy status was available for 22,101 participants. Apathy was present in 1,803 of 22,101 participants (8.16%). Follow-up ranged from 1 to 13 years. The combined odds ratio (OR) of cognitive impairment for patients with apathy was 2.07 (95% CI: 1.43-2.99; I2 = 86%), and the combined hazard ratio was 2.70 (95% CI: 1.38-5.27; I2 = 94%). The OR meta-analyses for different conversion outcomes were MCI (OR = 3.38, 95% CI: 1.57-7.28; I2 =71%), cognitive decline (OR = 1.27, 95% CI: 0.81-2.00; I2 = 64%) and dementia (OR = 2.12, 95% CI: 1.32-3.41; I2 = 86%). Subgroup analysis suggested that the association between apathy and cognitive impairment changed with age, depression adjustments, apathy measurement, and follow-up time. Conclusions: Apathy was associated with a greater than 2-fold increased risk of progression to cognitive impairment in the cognitively normal population. Future interventions targeting apathy management in the general population may reduce the risk of cognitive impairment.
| S-EPMC8721876 | biostudies-literature
Project description:BackgroundA dearth of differential research exists regarding the determinants of mild cognitive impairment (MCI) and moderate cognitive impairment or dementia among nursing home residents. This study aimed to identify and examine the association between medical factors (number of comorbidities, hospitalization, disability, depression, frailty and quality of life) and moderate cognitive impairment or dementia in nursing homes residents.MethodsA cross-sectional design was used in this study. Convenience sampling of 182 participants was conducted in nursing homes located in the central part of Jordan. Montreal cognitive assessment (MoCA) was used to screen both MCI and moderate cognitive impairment or dementia. Bivariate analysis, including t-test and ANOVA test, and logistic and linear regression models were used to examine and identify the medical factors associated with moderate cognitive impairment or dementia compared to mild cognitive impairment.ResultsMost nursing home residents had MCI (87.4%) compared to a few with moderate cognitive impairment or dementia. Age (t = - 2.773), number of comorbidities (t = - 4.045), depression (t = - 4.809), frailty (t = - 4.038), and quality of life physical (t = 3.282) and mental component summaries (t = 2.469) were significantly different between the stages of cognitive impairment. Marital status (t = - 4.050, p < 0.001), higher-income (t = 3.755, p < 0.001), recent hospitalization (t = 2.622,p = 0.01), depression (t = - 2.737, p = 0.007), and frailty (t = 2.852, p = 0.005) were significantly associated with mental ability scores among nursing home residents.ConclusionThe coexistence of comorbidities and depression among nursing home residents with MCI necessitates prompt management by healthcare providers to combat depressive symptoms in order to delay the dementia trajectory among at-risk residents.Trail registrationClinicalTrials.gov NCT04589637 , October 15,2020, Retrospectively registered.
| S-EPMC7672837 | biostudies-literature
Project description:BackgroundThere is a high degree of inter- and intra-individual variability observed within the phenotype of Down syndrome. The Down Syndrome Cognition Project was formed to capture this variability by developing a large nationwide database of cognitive, behavioral, health, and genetic information on individuals with Down syndrome, ages 6-25 years. The current study used the Down Syndrome Cognition Project database to characterize cognitive and behavioral variability among individuals with Down syndrome.MethodsLatent profile analysis was used to identify classes across a sample of 314 participants based on their cognition (IQ and executive functioning), adaptive and maladaptive behavior, and autism spectrum disorder symptomatology. A multivariate multinomial regression model simultaneously examined demographic correlates of class.ResultsResults supported a 3-class model. Each class demonstrated a unique profile across the subdomains of cognition and behavior. The "normative" class was the largest (n = 153, 48%) and displayed a relatively consistent profile of cognition and adaptive behavior, with low rates of maladaptive behavior and autism symptomatology. The "cognitive" class (n = 109, 35%) displayed low cognitive scores and adaptive behavior and more autism symptomatology, but with low rates of maladaptive behavior. The "behavioral" class, the smallest group (n = 52, 17%), demonstrated higher rates of maladaptive behavior and autism symptomatology, but with cognition levels similar to the "normative" class; their adaptive behavior scores fell in between the other two classes. Household income and sex were the only demographic variables to differ among classes.ConclusionsThese findings highlight the importance of subtyping the cognitive and behavioral phenotype among individuals with Down syndrome to identify more homogeneous classes for future intervention and etiologic studies. Results also demonstrate the feasibility of using latent profile analysis to distinguish subtypes in this population. Limitations and future directions are discussed.
| S-EPMC8056665 | biostudies-literature
Project description:Down Syndrome (DS) entails an increased risk of many chronic diseases that are typically associated with older age. The clinical manifestations of accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis has been sparse. Here, we utilize a quantitative molecular marker of aging (known as the epigenetic clock) to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue (on average by 6.6 years, P = 7.0 × 10(-14)).
| S-EPMC4406678 | biostudies-literature
Project description:Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age-associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Nowadays, due to the progressive advancements in social inclusion processes and medical assistance, DS persons live much longer than in the past; therefore, the early-onset health problems of these persons are becoming an urgent and largely unmet social and medical burden. In particular, the most important ailment of DS persons is the accelerated cognitive decline that starts when they reach about 40 years of age. This decline can be at least in part counteracted by multi-systemic approaches including early-onset cognitive training, physical activity, and psychosocial assistance. However, no pharmacological treatment is approved to counteract this decline. According to the most advanced conceptualization of Geroscience, tackling the molecular mechanisms underpinning the aging process should be a smart/feasible strategy to combat and/or delay the great majority of age-related diseases, including cognitive decline. We think that a debate is needed urgently on if (and how) this strategy could be integrated in protocols to face DS-associated dementia and overall unhealthy aging. In particular we propose that, on the basis of data obtained in different clinical settings, metformin is a promising candidate that could be exploited to counteract cognitive decline in DS.
| S-EPMC6516152 | biostudies-literature
Project description:Although subtle discourse declines in people with mild cognitive impairment (MCI) have been reported, heterogeneous measures and tasks among the MCI discourse studies have yielded widely varying outcomes. The present study aimed to first, identify discourse measures that aid the differentiation among people with amnestic MCI (aMCI), people with non-amnestic MCI (naMCI), and cognitively healthy control (HC) participants, and second, delineate the cognitive functions related to such discourse measures. Three discourse tasks (an episodic narrative, a planning task, and a picture description) were performed by 30 aMCI, 22 naMCI, and 21 HC participants. Samples were analyzed using six categories of 15 measures, namely coherence, cohesion, proposition, grammaticality, lexicality, and fluency. The statistical analyses included (1) a multivariate analysis of variance for group comparison; (2) binary simple logistic regression and receiver operating characteristic curve analysis for differentiation between two groups; (3) binary multiple logistic regression for being diagnosed with naMCI or aMCI with the minimum number of predictors; and (4) Pearson correlation analysis for identifying the cognitive functions associated with the discourse measures. The proportion of cohesive words and propositional density in aMCI participants were worse than those in naMCI participants. Global coherence, the proportion of cohesive words, and the proportion of dysfluencies and pauses in naMCI participants were lower than those in the HC participants. Global and local coherence and the proportion of cohesive words, cohesive ties per utterances, propositional density, and dysfluencies and pauses in aMCI participants were worse than those in the HC participants. The aforementioned measures were demonstrated to be effective predictors for classifying groups by receiver operating characteristic curve analysis. In addition, the proportions of cohesive words and pauses were common discourse measures for differentiation between naMCI and HC participants or between aMCI and HC participants using binary multiple logistic regression. According to the correlation analysis, memory and executive functions are needed for coherent, cohesive, and efficient discourse productions in MCI. The detailed description of discourse performances in this study will aid the characterization of the declined language abilities of MCI participants and also the understanding of the cognitive functions involved in discourse performance in MCI.
| S-EPMC6714864 | biostudies-literature
Project description:Down syndrome (DS) is the most frequent genetic cause of intellectual disability, characterized by alterations in different behavioral symptom domains: neurodevelopment, motor behavior, and cognition. As mouse models have the potential to generate data regarding the neurological basis for the specific behavioral profile of DS, and may indicate pharmacological treatments with the potential to affect their behavioral phenotype, it is important to be able to assess disease-relevant behavioral traits in animal models in order to provide biological plausibility to the potential findings. The field is at a juncture that requires assessments that may effectively translate the findings acquired in mouse models to humans with DS. In this article, behavioral tests are described that are relevant to the domains affected in DS. A neurodevelopmental behavioral screen, the balance beam test, and the Multivariate Concentric Square Field test to assess multiple behavioral phenotypes and locomotion are described, discussing the ways to merge these findings to more fully understand cognitive strengths and weaknesses in this population. New directions for approaches to cognitive assessment in mice and humans are discussed. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Preweaning neurodevelopmental battery Basic Protocol 2: Balance beam Basic Protocol 3: Multivariate concentric square field test (MCSF).
| S-EPMC7552827 | biostudies-literature
Project description:BackgroundPeople with Down syndrome (DS) are at high risk to develop Alzheimer's disease dementia (AD). Behavioral and psychological symptoms of dementia (BPSD) are common and may also serve as early signals for dementia. However, comprehensive evaluation scales for BPSD, adapted to DS, are lacking. Therefore, we previously developed the BPSD-DS scale to identify behavioral changes between the last six months and pre-existing life-long characteristic behavior.ObjectiveTo optimize and further study the scale (discriminative ability and reliability) in a large representative DS study population.MethodsOptimization was based on item irrelevance and clinical experiences obtained in the initial study. Using the shortened and refined BPSD-DS II, informant interviews were conducted to evaluate 524 individuals with DS grouped according to dementia status: no dementia (DS, N = 292), questionable dementia (DS + Q, N = 119), and clinically diagnosed dementia (DS + AD, N = 113).ResultsComparing item change scores between groups revealed prominent changes in frequency and severity for anxious, sleep-related, irritable, restless/stereotypic, apathetic, depressive, and eating/drinking behavior. For most items, the proportion of individuals displaying an increased frequency was highest in DS + AD, intermediate in DS + Q, and lowest in DS. For various items within sections about anxious, sleep-related, irritable, apathetic, and depressive behaviors, the proportion of individuals showing an increased frequency was already substantial in DS + Q, suggesting that these changes may serve as early signals of AD in DS. Reliability data were promising.ConclusionThe optimized scale yields largely similar results as obtained with the initial version. Systematically evaluating BPSD in DS may increase understanding of changes among caregivers and (timely) adaptation of care/treatment.
| S-EPMC8293661 | biostudies-literature
Project description:BACKGROUND:Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). There is an understanding that an increase in L-glutamate contributes to the pathogenesis of cerebral ischemias and AD. Memantine acts as an antagonist of N-methyl-D-aspartate (NMDA) type receptors, which is thought to reduce abnormal activation of glutamate neurotransmission. It binds with a low affinity to the NMDA receptor and so should not prevent learning and the formation of memory. Memantine can improve cognitive function and slow the decline of AD in the general population over time, and is the subject of this review. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. OBJECTIVES:To determine the effectiveness and safety of memantine for people with DS who develop AD. SEARCH STRATEGY:CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of memantine, as well as experts in the field, to ask about reports of unpublished or ongoing trials. SELECTION CRITERIA:Randomised controlled trials of participants with DS and AD in which treatment with memantine was administered compared with a placebo group. DATA COLLECTION AND ANALYSIS:No study was identified which met the inclusion criteria for this review. MAIN RESULTS:No study was identified which met inclusion criteria for this review, however there is an on-going randomised controlled study being conducted in the UK and data are expected in 2009. AUTHORS' CONCLUSIONS:As there are no included trials, recommendations cannot be made about memantine for AD in DS. Well-designed, adequately powered studies are required.
| S-EPMC7197456 | biostudies-literature